We have previously established the 1o structure and signaling properties of the human N-formyl peptide receptor (FPR), the FPRL1 receptor (FPRL= formyl peptide receptor like), the FPRL2 receptor and interleukin-8 receptor B (IL8RB) from cDNA and gene cloning. We have now defined the complete DNA sequence and structural organization of the human FPR gene including an analysis of its putative promoter sequence, and have proposed a mechanism for the molecular evolution of the FPR gene family. We have also extended our partial characterization of the genes for IL8RA, IL8RB and the IL8RB pseudogene. All of these genes lack introns in the coding block but have large introns separating the start points for transcription and translation. Furthermore, the 5'-untranslated region of the FPR gene resides on three alternatively spliced exons, a very unusual finding. We have also defined the sequence, ligand specificity, partial gene structure, expression and chromosomal localization of the first known receptor for a beta chemokine, the human MIP-1alpha/RANTES receptor which may mediate activation of both myeloid and lymphoid cells as well as regulate the proliferation of hematopoietic progenitors. A major finding from this work is that a putative receptor encoded by open reading frame US28 of human cytomegalovirus is 33% identical to the MIP-1alpha/RANTES receptor. Thus US28 may be an example of molecular mimicry by viral hijack of a host gene. We have shown that proteins involved in host defense functions are highly and exceptionally divergent between human and rodent species. A major new hypothesis was proposed to account for this phenomenon that has to do with molecular mimicry by acquisition of host genes by species-specific pathogens. New insights were also established regarding the molecular evolution of the ligand-receptor relationship.